Biochemistry of Nitric Oxide and Peroxynitrite: Sources, Targets and Biological Implications
Biochemistry of Nitric Oxide and Peroxynitrite: Sources, Targets and Biological Implications
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DOI：
10.1007/978-3-319-45865-6_5
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Radi, Rafael
中科院分区：
文献类型：
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作者：
Aicardo, Adrian;Martinez, Debora M.;Radi, Rafael
一氧化氮((NO)-N-中心点)是生物产生的一种相对稳定的自由基，参与了人体生物学中的一系列信号转导和生理过程。已有体内报道了(NO)-N-中心点的酶和非酶来源。在(NO)-N-中心点过度产生的情况下和/或在促氧化剂环境中，它可以转变为有毒分子，并转化为人类疾病的致病媒介。特别是，(NO)-N-中心点与超氧阴离子(O-2(中心点-))的扩散控制反应导致过氧亚硝酸根(ONOO-)的形成，ONOO-是一种强氧化剂和亲核剂，介导了与(NO)-N-中心点相关的大部分毒性。过氧亚硝酸盐通过一系列机制促进单电子和双电子氧化和硝化反应，其中一些涉及自由基中间体。在本章中，我们总结了(NO)-N-中心点、过氧亚硝酸根和其他活性氮物种(RNS)的形成机制、它们与生物分子靶标的反应以及参与病理发展的关键生化方面。此外，我们批判性地分析了目前基于氧化还原的治疗策略，包括化合物对(NO)-N-中心点和过氧亚硝酸根衍生的活性物种的直接作用以及诱导或内源性抗氧化机制，总体目标是应对亚硝酸应激条件。
Nitric oxide ((NO)-N-center dot) is a relatively stable free radical generated biologically that participates in a series of signal transducing and physiological processes in human biology. Enzymatic as well as non-enzymatic sources of (NO)-N-center dot have been reported in vivo. In circumstances where (NO)-N-center dot is overproduced and/or in the context of a pro-oxidant environment, it can turn into a toxic molecule and converts into a pathogenic mediator in human diseases. In particular, the diffusion-controlled reaction of (NO)-N-center dot with superoxide radical anion (O-2(center dot-)) leads to the formation of peroxynitrite (ONOO-), a strong oxidant and nucleophile that mediates much of the toxicity associated to (NO)-N-center dot. Peroxynitrite promotes one- and two-electron oxidations and nitration reactions via a series of mechanisms several of which involve free radical intermediates. In this chapter we summarize key biochemical aspects concerning the mechanisms of formation of (NO)-N-center dot, peroxynitrite and other reactive nitrogen species (RNS), their reaction with biomolecular targets and participation in the development of pathologies. In addition, we critically analyze current redox-based therapeutic strategies including the direct action of compounds on (NO)-N-center dot-and peroxynitrite-derived reactive species as well as the induction or endogenous antioxidant mechanisms, with the overall goal to cope against nitroxidative stress conditions.